E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
CP-CML patients with non hematologic low toxicity grade to imatinib |
|
E.1.1.1 | Medical condition in easily understood language |
Patient affected by Chronic Phase Chronic Myeloid Leukemia under imatinib treatment who have mild toxic reactions not in the blood to imatinib |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10054352 |
E.1.2 | Term | Chronic phase chronic myeloid leukemia |
E.1.2 | System Organ Class | 100000004864 |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of this study is to assess the frequency of reduction in grade
(Grade 2 to 1) or resolution of imatinib-related chronic Grade 1 or Grade 2
non-hematologic AEs within 3 months after switch to dasatinib in patients with CP-CML. |
|
E.2.2 | Secondary objectives of the trial |
- Frequency of dasatinib-related AEs
• Mean change in M.D. Anderson Symptom Inventory-Chronic Myeloid Leukemia
(MDASI-CML) symptom severity and interference score from baseline to 3, 6, and
12 months after switch to dasatinib
• Mean change in EORTC-Quality of Life Questionnaire (EORTC-QLQ-C30) score
from baseline to 6 and 12 months after switch to dasatinib
• Proportion of patients with reduction in grade (Grade 2 to 1) or resolution of at least 1
imatinib-related chronic Grade 1 or Grade 2 non-hematologic adverse event within
3 months after switch to dasatinib, without an increase in grade of any
imatinib-related, chronic, Grade 1 or 2, non-hematologic adverse event |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- signed Informed
- Subjects with CP-CML achieving an optimal response (either CHR by 3 months,
PCyR by 6 months, or CCyR by 12 months) to imatinib ≤ 400 mg/day treatment
- Currently experiencing at least one imatinib-related Grade 1 or 2 non-hematologic
adverse event persisting for at least 2 months or recurring at least 3 times in the
preceding 12 months, despite best supportive care
Daily ECOG performance status = 0 – 2
- Life expectancy >6 months
- Adequate renal function defined as serum creatinine ≤ 3 times the institutional
ULN
- Adequate hepatic function defined as: total bilirubin ≤ 3.0 times the institutional
ULN; alanine aminotransferase (ALT) and aspartate aminotransferase
(AST) ≤ 5.0 times the institutional upper limit of normal (ULN)
- Serum Na, K, Mg, and total serum Ca or ionized Ca levels must be greater than or
equal to the institutional lower limit of normal. Subjects with low K, Mg levels,
total serum Ca and/or ionized Ca must be repleted to allow for protocol entry.
- Men and women, ages 18 or older
- Women of childbearing potential (WOCBP) must use highly effective methods of
birth control to minimize the risk of pregnancy. WOCBP must follow instructions
for birth control for the entire duration of the study including a minimum of 1
month (4 weeks) after dosing has been completed.
Acceptable methods of highly effective birth control include:
• Condom with spermicide
• Diaphragm and spermicide
• Cervical cap and spermicide
The use of intrauterine devices, (IUDs) shall be at the discretion of the
investigator.
Women must have a negative serum or urine pregnancy test (minimum
sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to the
start of investigational product.
- Women must not be breastfeeding
- Sexually active fertile men must use highly effective birth control if their partners
are WOCBP. Men that are sexually active with WOCBP must follow instructions
for birth control for the entire duration of the study and a minimum of 1 month
(4 weeks) after dosing has been completed. |
|
E.4 | Principal exclusion criteria |
- Previous treatment with any other TKI, except imatinib
- Current Grade 3 or 4 imatinib-related adverse event
- Subjects with clonal evolution in Ph+ cells observed in ≥ 2 metaphases at baseline
bone marrow (BM) cytogenetic test, unless the same abnormalities were present
at diagnosis (See Section 5.8.2 for subjects exempt from baseline bone marrow
cytogenetic assessment)
- Subjects with previous loss of CHR or loss of major cytogenetic response
(MCyR) on imatinib
- Previous diagnosis of accelerated or blast phase CML
- A serious uncontrolled medical disorder or active infection that would impair the
ability of the subject to receive protocol therapy
- Uncontrolled or significant cardiovascular disease, including any of the following:
i. Congestive cardiac failure (NYHA > 2) within 3 months
ii. Diagnosed or suspected congenital long QT syndrome
iii. Any history of clinically significant ventricular arrhythmias
iv. Prolonged QTcF interval on pre-entry electrocardiogram (> 450 msec)
v. Any history of second or third degree heart block (may be eligible if the subject currently has a pacemaker)
vi. Uncontrolled angina within 3 months
vii. Prior myocardial infarction within 6 months
viii. Uncontrolled hypertension
- Known pulmonary arterial hypertension
- Pleural or pericardial effusions of any grade at study entry are excluded. Subjects
previously diagnosed with pleural/pericardial effusion of any grade resolved at the
time of study entry are allowed
- History of significant bleeding disorder unrelated to CML, including
i. Diagnosed congenital bleeding disorders (eg, von Willebrand’s disease)
ii. Diagnosed acquired bleeding disorder within one year (eg, acquired antifactor
VIII antibodies)
- Serious mental illness interfering with the ability to participate in the study
- Prior documented T315I mutation (Enrollment is not dependent upon results of
baseline mutation analysis)
- Patients who are pregnant or breastfeeding or likely to become pregnant
- Men whose partner is unwilling or unable to avoid pregnancy
- Prisoners or subjects who are involuntarily incarcerated
- Subjects who are compulsorily detained for treatment of either a psychiatric or
physical (eg, infectious disease) illness.
- Subjects unable to complete patient-reported outcomes without assistance |
|
E.5 End points |
E.5.1 | Primary end point(s) |
To assess the rate of MMR after the switch to dasatinib |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
at 6 and 12 months after the switch to dasatinib |
|
E.5.2 | Secondary end point(s) |
To assess the rate of MR after the switch to dasatinib |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
at 6 and 12 months after the switch to dasatinib |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 12 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
France |
Italy |
Germany |
Korea, Republic of |
United States |
|
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |